Several quantitation approaches have been tried to measure nicotine levels in plasma. Primarily, gas chromatographic approaches tried conventional and microbore columns with flame and alkali flame detectors, and the liquid chromatographic techniques employed both normal and reverse phase systems with and without ion-pairs using UV and EC detectors. We have not been successful in establishing a method that requires a 1-2 ng/ml sensitivity. We are presently exploring a capillary GC with NP detector which appears to show great promise.